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N Sadato

Publications and source records attributed to N Sadato.

At least 55 records · Page 3Linked to original sources

Verb generation in Japanese--A multicenter PET activation study.

Cerebral blood flow (CBF) during silent verb generation was measured at four Japanese PET centers. To minimize the variance of the measurement, speakers of a single language (Japanese) served as subjects and experimental conditions at the four PET centers were controlled as much as possible. Two types of activation patterns were observed: activations in the left dorsolateral prefrontal cortices and the medial frontal cortex (at the two centers with a 2D PET scanner) and additional activation in the left posterior temporal cortex (at the two centers with a 3D scanner). This suggests either a difference in the sensitivity of the two types of PET scanners (viz., a 3D scanner is generally more sensitive than a 2D scanner) and/or subject bias due to the small number of subjects at the individual centers. The pooled activation pattern was fundamentally similar to activation patterns obtained in the previous studies for verb generation in English and other European languages, suggesting that regions for verb generation are independent of particular languages. Regions relevant to verb generation are discussed.

Adult↗

Prediction of improvement of cerebral perfusion with I-123 iomazenil SPECT.

We report a case of 61-year old man who was suffering from cerebrovascular disease with right hemiparesis and received I-123 iomazenil (IMZ) SPECT prior to carotid endoarterectomy. Severe stenosis of the right internal carotid artery and occlusion of the left middle cerebral artery (MCA) were revealed by cerebral angiography, and a hypoperfused area in left MCA territory and crossed cerebellar diaschisis (CCD) on I-123 IMP SPECT was demonstrated. In contrast, IMZ SPECT showed symmetric normal distribution. After the carotid endoarterectomy, the hypoperfused area in left MCA territory on IMP SPECT and hemiparesis had improved. It is thought that IMZ SPECT can be a useful tool for the prediction of improvement of cerebral perfusion and the clinical outcome.

Arterial Occlusive Diseases↗

A trial for the quantification of regional myocardial blood flow with continuous infusion of Tc-99m MIBI and dynamic SPECT.

UNLABELLED: We propose a new method to quantify regional myocardial blood flow (rMBF) by continuous infusion of Tc-99m MIBI and dynamic SPECT. METHODS: Five patients with old myocardial infarction were studied. During continuous infusion of MIBI (approximately 740 MBq) with a syringe pump in 10 min, dynamic SPECT scan was performed every minute and lasted 20 min after the start of infusion to identify myocardial uptake of MIBI. Input function was obtained from the radioactivity in the left ventricle (LV) in dynamic SPECT images. Spillover fraction between LV and myocardium (M) was corrected with phantom data. The influx constant (Ku) was calculated by Patlak plot graphical analysis, and compared with rMBF measured by PET (F) with N-13 ammonia based on Patlak plot analysis with correction for the extraction fraction. To correct the limited first-pass extraction of MIBI, linearization correction by means of the permeability-surface area (PS) product value was also applied. RESULTS: Spillover fractions of MIBI were 0.169+/-0.056 from LV to M, and 0.042+/-0.021 from M to LV. Ku was well correlated with F (Ku = 0.057 + 0.220F, r = 0.83, p < 0.01) and the slope and correlation were improved after linearizaiton (F(MIBI) = -0.131+0.858F, r = 0.94, p < 0.01). CONCLUSION: The proposed method has the potential to be a clinically feasible tool for quantitative measurement of rMBF.

Aged↗

Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by positron autoradiography.

Fresh rat brain slices were incubated with 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [18F]FDG uptake were obtained from these specimens on imaging plates. The fractional rate constant (= k3*) of [18F]FDG proportional to the cerebral glucose metabolic rate (CMRglc) was evaluated by applying the Gjedde-Patlak graphical method to the image data. With hypoxia loading (oxygen deprivation) or glucose metabolism inhibitors acting on oxidative phosphorylation, the k3* value increased dramatically suggesting enhanced glycolysis. After relieving hypoxia < or = 10-min, the k3* value returned to the pre-loading level. In contrast, with > or = 20-min hypoxia only partial or no recovery was observed, indicating that irreversible neuronal damage had been induced. However, after loading with tetrodotoxin (TTX), the k3* value also decreased but returned to the pre-loading level even after 70-min TTX-loading, reflecting a transient inhibition of neuronal activity. This technique provides a new means of quantifying dynamic changes in the regional CMRglc in living brain slices in response to various interventions such as hypoxia and neurotoxic chemical-loading as well as determining the viability and prognosis of brain tissues.

Animals↗

Neuronal substrates participating in attentional set-shifting of rules for visually guided motor selection: a functional magnetic resonance imaging investigation.

To investigate the neuronal substrates participating in attentional set-shifting for motor selection rules, a functional magnetic resonance imaging study was performed during hand-shape selection tasks. During the session, six right-handed subjects were required to make one of three hand-shapes using their right hands, in response to the hand-shape images on a video screen, following one of the three predefined rules of win, lose, and tie. The selection rules were consistently applied in three conditions (win, tie, and lose), and changed alternately in one condition (alternate win-lose). Thus the alternate win-lose condition requires the shift of rules for motor selection. This alternate condition compared with the win, tie, and lose conditions showed activation in the left middle frontal gyrus, the bilateral inferior frontal gyri, and the left posterior fusiform and lingual gyri. These activation patterns in the prefrontal cortex were similar to those observed during the performance of the Wisconsin Card Sorting Test (WCST), which requires a typical set-shifting ability from one perceptual dimension to another (Berman et al., 1995. Neuropsychologia 33, 1027-1046; Nagahama et al., 1996. Brain 119, 1667-1675; Konishi et al., 1998. Nature Neuroscience 1, 80-84.). Our data may indicate that the dorsolateral prefrontal cortex including the middle and inferior frontal gyri are important in attentional set-shifting of both perceptual and non-perceptual characteristics. Another activation in the fusiform and lingual gyri may have reflected the increased attentional demand for visual processing in the light of a current rule for motor selection.

Adult↗

Brain structures related to active and passive finger movements in man.

A PET study was performed in six normal volunteers to elucidate the functional localization of the sensory afferent component during finger movement. Brain activation during the passive movement driven by a servo-motor was compared with that during an auditory-cued active movement which was controlled kinematically in the same way as the passive one. A newly developed device was used for selectively activating proprioception with a minimal contribution from tactile senses. Active movement was associated with activation of multiple areas, including the contralateral primary sensorimotor cortex, premotor cortex, supplementary motor area (SMA), bilateral secondary somatosensory areas and basal ganglia and ipsilateral cerebellum. In contrast, only the contralateral primary and secondary somatosensory areas were activated by the passive movement. It is likely that the contribution of proprioceptive input to the activation of the premotor cortex, SMA, cerebellum and basal ganglia, if any, is small. However, the present results do not rule out the possibility that the cutaneous afferent input or the combination of cutaneous and proprioceptive input participates in the activation of those areas during the active movement.

Acoustic Stimulation↗

The increased accumulation of [18F]fluorodeoxyglucose in untreated prostate cancer.

BACKGROUND: To evaluate the clinical usefulness of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) compared with histopathological grading, clinical stage and serum prostatic specific antigen (PSA) level in the detection and characterization of prostate cancer. METHODS: Forty-four patients with histologically proven prostate cancer and five control subjects with benign prostatic hyperplasia (BPH) were prospectively investigated with FDG-PET prior to treatment. RESULTS: By visual inspection, FDG accumulation was positive in 28 patients with prostate cancer (sensitivity 64%), whereas all were negative in the control group. FDG-PET in three patients with lymph node metastases did not show any high intrapelvic accumulations corresponding to metastatic sites. Among 12 patients with multiple bone metastases which were detected with 99m-HMDP bone scintigraphy, nine (75%) showed moderate to high FDG accumulation at the sites of bone metastases. Quantitatively, FDG accumulation in prostate cancer was significantly higher than in BPH and there was a tendency for FDG uptake of tumors to be higher with higher histological Gleason grades. Furthermore, FDG uptake in tumors with lymph node and/or bone metastasis was significantly higher than that of localized stages. However, the correlation between PSA and FDG uptake in the prostate cancer was very weak for clinical relevance. CONCLUSIONS: Although FDG-PET was not sensitive enough to detect prostate cancer in clinical use, it is suggested that glucose metabolism in prostate cancer tended to be higher in patients with tumors of advanced stages.

Aged↗

Crossed cerebellar diaschisis: assessment with dynamic susceptibility contrast MR imaging.

The authors investigated the feasibility of using T2-weighted, half-Fourier rapid acquisition with relaxation enhancement, or RARE, dynamic susceptibility contrast magnetic resonance (MR) imaging to depict crossed cerebellar diaschisis. In 10 patients after unilateral supratentorial stroke, crossed cerebellar diaschisis was demonstrated in the relative regional cerebellar blood volume maps obtained with MR imaging. Cerebellar blood volume values for the nonaffected cerebellar hemisphere were significantly larger than those for the affected side (P = .0003).

Algorithms↗

Mesial motor areas in self-initiated versus externally triggered movements examined with fMRI: effect of movement type and rate.

The human frontomesial cortex reportedly contains at least four cortical areas that are involved in motor control: the anterior supplementary motor area (pre-SMA), the posterior SMA (SMA proper, or SMA), and, in the anterior cingulate cortex, the rostral cingulate zone (RCZ) and the caudal cingulate zone (CCZ). We used functional magnetic resonance imaging (fMRI) to examine the role of each of these mesial motor areas in self-initiated and visually triggered movements. Healthy subjects performed self-initiated movements of the right fingers (self-initiated task, SI). Each movement elicited a visual signal that was recorded. The recorded sequence of visual signals was played back, and the subjects moved the right fingers in response to each signal (visually triggered task, VT). There were two types of movements: repetitive (FIXED) or sequential (SEQUENCE), performed at two different rates: SLOW or FAST. The four regions of interest (pre-SMA, SMA, RCZ, CCZ) were traced on a high-resolution MRI of each subject's brain. Descriptive analysis, consisting of individual assessment of significant activation, revealed a bilateral activation in the four mesial structures for all movement conditions, but SI movements were more efficient than VT movements. The more complex and more rapid the movements, the smaller the difference in activation efficiency between the SI and the VT tasks, which indicated an additional processing role of the mesial motor areas involving both the type and rate of movements. Quantitative analysis was performed on the spatial extent of the area activated and the percentage of change in signal amplitude. In the pre-SMA, activation was more extensive for SI than for VT movements, and for fast than for slow movements; the extent of activation was larger in the ipsilateral pre-SMA. In the SMA, the difference was not significant in the extent and magnitude of activation between SI and VT movements, but activation was more extensive for sequential than for fixed movements. In the RCZ and CCZ, both the extent and magnitude of activation were larger for SI than for VT movements. In the CCZ, both indices of activation were also larger for sequential than for fixed movements, and for fast than for slow movements. These data suggest functional specificities of the frontomesial motor areas with respect not only to the mode of movement initiation (self-initiated or externally triggered) but also to the movement type and rate.

Adult↗

Anatomic validation of spatial normalization methods for PET.

UNLABELLED: Spatial normalization methods, which are indispensable for intersubject analysis in current PET studies, have been improved in many aspects. These methods have not necessarily been evaluated as anatomic normalization methods because PET images are functional images. However, in view of the close relation between brain function and morphology, it is very intriguing how precisely normalized brains coincide with each other. In this report, the anatomic precision of spatial normalization is validated with three different methods. METHODS: Four PET centers in Japan participated in this study. In each center, six normal subjects were recruited for both H2(15)O-PET and high-resolution MRI studies. Variations in the location of the anterior commissure (AC) and size and contours of the brain and the courses of major sulci were measured in spatially normalized MR images for each method. Spatial normalization was performed as follows. (a) Linear: The AC-posterior commissure and midsagittal plane were identified on MRI and the size of the brain was adjusted to the Talairach space in each axis using linear parameters. (b) Human brain atlas (HBA): Atlas structures were manually adjusted to MRI to determine linear and nonlinear transformation parameters and then MRI was transformed with the inverse of these parameters. (c) Statistical parametric mapping (SPM) 95: PET images were transformed into the template PET image with linear and nonlinear parameters in a least-squares manner. Then, coregistered MR images were transformed with the same parameters used for the PET transformation. RESULTS: The AC was well registered in all methods. The size of the brain normalized with SPM95 varied to a greater extent than with other approaches. Larger variance in contours was observed with the linear method. Only SPM95 showed significant superiority to the linear method when the courses of major sulci were compared. CONCLUSION: The results of this study indicate that SPM95 is as effective a spatial normalization as HBA, although it does not use anatomic images. Large variance in structures other than the AC and size of the brain in the linear method suggests the necessity of nonlinear transformations for effective spatial normalization. Operator dependency of HBA also must be considered.

Brain↗

[Phase 1 clinical study of 123I-IBF, a new radioligand for evaluating dopamine D2 receptor with SPECT (I); biodistribution and dosimetry].

A Phase 1 clinical study of 123I-IBF, (S)-5-iodo-7- N-[(1-ethyl-2-pyrrolidinyl)methyl]carboxamido-2,3-dihydrobenzofuran, developed for evaluation of dopamine D2 receptor (D2-R) with SPECT, was performed in 12 healthy male volunteers. No side effects due to 123I-IBF (i.v. 167 MBq) injection were observed. In sequential whole-body images, the radioactivity was distributed mainly in the liver, lungs and brain, and decreased gradually. No significant retention of radioactivity was seen in any organ at 24 hr after injection. The absorbed dose of 123I-IBF, calculated based on the whole-body pharmacokinetics, was equal to or less than those of other brain perfusion imaging agents. No significant problems were observed in terms of the safety, pharmacokinetics or absorbed dose of 123I-IBF.

Adult↗

[Phase 1 clinical study of 123I-IBF, a new radioligand for evaluating Dopamine D2 receptor with SPECT (II); pharmacokinetics study and quantification in the brain].

The pharmacokinetics of (S)-5-iodo-7-N-[(1-ethyl- 2-pyrrolidinyl)methyl]carboxamido-2,3-dihydro-benzofuran (123I-IBF) in the brain were studied in 12 healthy male volunteers as a Phase I clinical study. The striatum-to-frontal cortex count ratio (-1) (St/Fc-1), which is a semi-quantitative index of the binding potential of 123I-IBF reached 1.81 +/- 0.19 and 2.21 +/- 0.39 at 90-120 min and 180-210 min after intravenous injection of 123I-IBF. St/Fc-1 obtained by SPECT at these times correlated well with the distribution volume ratio (-1) (Vd(St)/Vd(Fc)-1) based on three-compartment model analysis using an input function obtained by intermittent arterial sampling. The binding potential (BPR), calculated by the curve-fitting method using the time-activity curve in the reference region, also correlated well with the Vd(St)/ Vd(Fc)-1. The intra-observer and inter-observer reproducibilities of the striatum-to-cerebral cortex count ratios obtained using fixed-shape regions of interest (template ROIs) were superior to those obtained using manual ROIs. These results suggest that 123I-IBF is a promising agent for non-invasive quantification of the dopamine D2 receptor (D2-R) binding potential by SPECT.

Adult↗

Hyperacute changes in glucose metabolism of brain tumors after stereotactic radiosurgery: a PET study.

UNLABELLED: Cultured tumor cells show a marked increase in deoxyglucose uptake as early as 3 h after single high-dose irradiation, reflecting hyperacute response of the cells to noxious intervention. To evaluate the hyperacute effect of high-dose irradiation on tumor glucose metabolism in vivo, we measured 2-[18F]fluoro-2-deoxy-D-glucose (FDG) tumor uptake before and immediately after stereotactic radiosurgery. METHODS: A total of 19 brain tumors (17 metastatic and 2 primary, a meningioma and a central neurocytoma) in eight patients were treated with stereotactic radiosurgery. The received dose was between 24 and 32 Gy delivered to the central target point in the tumor. FDG PET was performed within 1 wk before radiosurgery and again 4 h after treatment. The net influx constant (Ki) was calculated on a pixel-by-pixel basis using graphical analysis, and the Ki ratio of tumor to ipsilateral cerebellum was used as an index of FDG uptake of the tumor. RESULTS: Eighteen of 19 irradiated tumors, all metastatic tumors and the meningioma, showed a 29.7% +/- 14.0% increase in the Ki ratio, which was significantly higher than that of nonirradiated tumors (4.1% +/- 3.6%, n = 8, P < 0.0001, analysis of variance). In metastatic tumors, an increase in the Ki ratio was significantly correlated with a decrease in the size of the irradiated tumors, as revealed by follow-up with CT or MRI (r = 0.61, P = 0.012, simple regression). The meningioma did not show a significant decrease in size, probably due to the short follow-up period. The central neurocytoma did not show any change in the Ki ratio or in tumor size. CONCLUSION: Serial FDG PET could be a potential tool for predicting the outcome of radiosurgery for brain tumors by detecting hyperacute changes in tumor glucose metabolism.

Brain↗

FDG PET to evaluate combined intra-arterial chemotherapy and radiotherapy of head and neck neoplasms.

UNLABELLED: We evaluated the effectiveness of combined intra-arterial chemotherapy and radiotherapy on head and neck squamous cell carcinomas using fluorodeoxyglucose (FDG) PET. METHODS: Fifteen patients with squamous cell carcinoma of the head and neck were included in the study. Fourteen patients completed the treatment regimen and underwent FDG PET before and 4 wk after chemoradiotherapy. One patient underwent pretreatment FDG PET only. The pretreatment and post-treatment PET images were compared with clinical and histopathologic evaluations of the effects of chemoradiotherapy. For the quantitative evaluation of regional radioactivity, standardized uptake values (SUVs) with an uptake period of 50 min were used. RESULTS: Before treatment, FDG PET detected neoplasms in all 15 patients. The overall clinical response rate to chemoradiotherapy in the 14 patients who were imaged before and after treatment was 100%. Before treatment, the neoplastic lesions showed high SUVs (mean 7.77 mg/mL), which significantly decreased after therapy (3.62 mg/mL, P < 0.01). Lesions with higher pretreatment SUVs (> 7 mg/mL) showed residual viable tumor cells after the treatment in 3 of 8 patients, whereas those with lower SUVs (< 7 mg/mL, 6 patients) were successfully treated. Three of seven tumors with post-treatment SUVs > 4 mg/mL had viable tumor cells, whereas all tumors (7/7) with post-treatment SUVs < 4 mg/mL showed no viable cells. With concomitant chemoradiotherapy monitored by FDG PET, 5 patients avoided surgery entirely, and the remaining 9 patients underwent a reduced form of surgery. CONCLUSION: FDG PET is useful in evaluating the effects of combined chemotherapy and radiotherapy in patients with head and neck carcinoma. Pretreatment FDG PET is useful in predicting the response to treatment, and post-treatment FDG PET can evaluate residual viable cells. Hence, FDG PET is a valuable tool in the treatment of head and neck tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Noninvasive measurement of cerebral metabolic rate of glucose using standardized input function.

UNLABELLED: The purpose of this study was to propose and validate a method for the noninvasive measurement of cerebral metabolic rate of glucose (CMRGlc) by fluorodeoxyglucose (FDG) PET with a standardized input function (SIF) and an autoradiographic method. METHODS: Plasma input functions, measured by intermittent arterial blood samplings after the intravenous injection of FDG, in 44 patients who had fasted for at least 6 h, were used to generate the SIF. The input function of each patient was normalized with the net injected dose (nID) of FDG and body mass as indicated by body surface area (BSA) or body weight (BW). The SIF was generated as an average of 44 normalized input functions. The estimation of the input function and CMRGlc with SIF was validated in 10 additional patients, who underwent FDG PET after fasting for at least 6 h. CMRGlc was estimated with a simulated input function (IFsim) generated with the following equation: IFsim = SIF x (nID/body mass). The estimated CMRGlc was compared with the measured CMRGlc. RESULTS: Based on BSA, the percentage error of the area under the curve of IFsim was 3.5%+/-2.2%. The percentage error of CMRGlc was 2.9%+/-1.9% in gray matter and 3.4%+/-2.2% in white matter. A similar percentage error was obtained based on BW. CONCLUSION: The proposed method is noninvasive and accurate, and therefore is clinically acceptable for measuring CMRGlc in patients in fasting states.

Autoradiography↗

Neural activity during attention shifts between object features.

To investigate the neural mechanisms involved in shifting attention we used positron emission tomography to examine regional cerebral blood flow (rCBF) during a task that demands shifting attention between color and shape. Significant activation was observed in the right dorsal prefrontal cortex and parieto-occipital cortex at all frequencies of attention shifts. The frequency of shifts between categories correlated significantly with rCBF in the rostral part of the supplementary motor area and the left precuneus, whereas the number of successive correct responses correlated with rCBF in the orbitofrontal cortex and the caudate nucleus. This study suggests that several prefrontal regions may participate in the processes of shifting attention in different ways.

Adult↗

Dynamic changes in glucose metabolism by lactate loading as revealed by a positron autoradiography technique using rat living brain slices.

To demonstrate the preference of lactate over glucose as an energy substrate in normal brain tissue under normoxic condition, the dynamic changes in glucose uptake by lactate loading were investigated in living rat brain slices using a positron autoradiography technique. Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution containing 10 mM glucose at 36 degrees C. During incubation, serial two-dimensional imaging of [18F]FDG uptake in the slices was constructed on the imaging plates. Lactate loading (20 mM) reversibly suppressed the [18F]FDG accumulation up to 80 min. Compared with the pre-loading and the unloaded control values, [18F]FDG uptake was suppressed to 25-45% in cerebral regions and 6-7% in cerebellum. The lactate concentration in the surrounding medium decreased after lactate loading. Hence brain tissue preferentially uses lactate over glucose under normoxic and euglycemic condition.

Animals↗

Neural networks for generation and suppression of alpha rhythm: a PET study.

To study neuronal activities that influence the generation of the alpha rhythm, we used positron emission tomography and simultaneous recording of the electroencephalogram (EEG) in normal volunteers and under passive conditions. A negative correlation between regional cerebral blood flow and alpha power was found in the occipital cortex, consistent with the visual modality-specific reactivity of the alpha rhythm. A positive correlation was found in the pons, midbrain, hypothalamus, amygdala, the basal prefrontal cortex, insula and the right dorsal premotor cortex. Neuronal activities of the brain stem and limbic system that are positively correlated with alpha power may provide an anatomical basis for studies of the relationship between emotional state and brain rhythm in health and disease.

Adult↗